Mitochondrial dysfunction (MD) is linked to cardiometabolic complications, such as obesity and insulin resistance (IR), the frequencies of which are higher in adults living with HIV infection and receiving combination antiretroviral therapies (ARV). ARV-treated youth living with perinatally acquired HIV infection (YLPHIV) may be especially susceptible to IR due to long-term exposure to both factors. Medical histories, fasting blood chemistry panels, and mitochondrial function in banked peripheral blood mononuclear cells (PBMCs) were assessed in eligible YLPHIV from the Pediatric HIV/AIDS Cohort Study (PHACS)/Adolescent Master Protocol (AMP) Mitochondrial Determinants Component cohort, stratified by Homeostatic Model Assessment of IR (HOMA-IR) score: case (score ≥4, n = 39) or control (score <4, n = 105). PBMCs were sources for mitochondrial (mt) DNA copies/cell; mtRNA transcript levels of oxidative phosphorylation (OXPHOS) subunits NADH dehydrogenases 1 and 6, and cytochrome B; and enzymatic activities of OXPHOS Complexes I (CI) and IV (CIV). Logistic regression models were fit to estimate the odds of IR case diagnosis, adjusted for sex, race/ethnicity, body mass index (BMI) z-score, and Tanner stage. IR cases were similar to controls by age, sex, and race/ethnicity. Cases had higher median levels of peak HIV viral load, lactate, pyruvate, triglycerides, and BMI z-scores. OXPHOS CI enzymatic activity was lower in cases (log₁₀ 1.62 vs. 1.70) and inversely correlated with HOMA-IR score (r = −0.157, p = .061), but did not associate with IR in adjusted models. Fully adjusted models indicated associations of nadir CD4% [odds ratio (OR) = 0.95, 95% confidence intervals (CIs) = 0.90–1.00] or peak HIV load (OR = 3.48, 95% CIs = 1.70–10.79) with IR. IR in YLPHIV was strongly associated with morphometrics, but early virologic and immunologic factors may also influence MD.

中文翻译：

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围产期感染 HIV 的青春期青年的线粒体功能障碍和胰岛素抵抗。

线粒体功能障碍 (MD) 与心脏代谢并发症有关，例如肥胖和胰岛素抵抗 (IR)，在感染 HIV 并接受联合抗逆转录病毒疗法 (ARV) 的成年人中，这些并发症的发生率更高。由于长期暴露于这两种因素，接受 ARV 治疗的围产期获得性 HIV 感染 (YLPHIV) 青年可能特别容易受到 IR 的影响。在符合条件的 YLPHIV 中评估了来自儿科 HIV/AIDS 队列研究 (PHACS)/青少年主协议 (AMP) 线粒体决定因素组分队列的病史、空腹血液化学组和储存外周血单个核细胞 (PBMC) 的线粒体功能，并按以下因素分层IR（HOMA-IR）的稳态模型评估得分：情况（得分≥4，ñ  = 39）或对照（评分<4，ñ = 105）。PBMC 是线粒体 (mt) DNA 拷贝/细胞的来源；氧化磷酸化 (OXPHOS) 亚基 NADH 脱氢酶 1 和 6 以及细胞色素 B 的 mtRNA 转录水平；OXPHOS 复合物 I (CI) 和 IV (CIV) 的酶活性。逻辑回归模型适用于估计 IR 病例诊断的几率，并根据性别、种族/民族、体重指数 (BMI) z 分数和 Tanner 分期进行调整。IR 病例与年龄、性别和种族/民族的对照相似。病例的 HIV 病毒载量峰值、乳酸、丙酮酸、甘油三酯和 BMI z 值的中位数水平较高。OXPHOS CI 酶活性在病例中较低（log ₁₀ 1.62 vs. 1.70）并且与 HOMA-IR 评分呈负相关（r  = -0.157，p = .061)，但在调整后的模型中与 IR 无关。完全调整的模型表明最低点 CD4% [优势比 (OR) = 0.95，95% 置信区间 (CI) = 0.90–1.00] 或峰值 HIV 载量 (OR = 3.48, 95% CI = 1.70–10.79) 与 IR 之间的关联。YLPHIV 中的 IR 与形态计量学密切相关，但早期病毒学和免疫学因素也可能影响 MD。